Synthetic methodologies for the construction of novel nucleoside derivatives with potential antiviral and anticancer activity

构建具有潜在抗病毒和抗癌活性的新型核苷衍生物的合成方法

• 批准号: 507457-2016
• 负责人: Snieckus, Victor
• 金额: $ 4.3万
• 依托单位: Queen's University
• 依托单位国家: 加拿大
• 项目类别: Collaborative Research and Development Grants
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=618942
• 关键词: Synthetic; methodologies; construction; novel; nucleoside

Nucleosides and nucleotides are essential biomolecules for the functioning of cellular systems in all living organisms. Both nucleosides and nucleotides have been developed as drug molecules, but nucleosides possess enhanced physicochemical properties that allow them to penetrate cell membranes. Moreover, nucleosides are readily converted into active nucleotides via cellular phosphorylation processes, such as cell signaling, DNA and RNA synthesis, enzyme regulation and metabolism. Therefore, new and improved synthetic routes for nucleosides are of considerable interest in drug discovery programs of and will benefit many Canadian and international pharmaceutical companies. This research proposal aims to develop efficient synthetic methods for the preparation of nucleoside analogues bearing original features such as: a) introduction of functional groups at the 1' position and b) conformational restriction of the sugar backbone. The introduction of these structural elements will provide opportunities for novel interactions with biological targets of interest in the fields of anticancer and antiviral drug discovery. By targeting such nucleosides, this collaboration will lead to low-cost and locally produced medicines for Canadians, all while aiding to develop young scientific minds that would otherwise not have the opportunity to participate in high-impact industrial collaborations at the undergraduate level.

核苷和核苷酸是所有生物体中细胞系统功能的基本生物分子。核苷和核苷酸都已被开发为药物分子，但核苷具有增强的物理化学性质，使它们能够穿透细胞膜。此外，核苷很容易通过细胞磷酸化过程转化为活性核苷酸，如细胞信号传导、DNA和RNA合成、酶调节和代谢。因此，新的和改进的核苷合成路线在药物发现计划中具有相当大的兴趣，并将使许多加拿大和国际制药公司受益。本研究计划旨在开发有效的合成方法，用于制备具有原始特征的核苷类似物，例如：a）在1'位引入官能团和B）糖骨架的构象限制。这些结构元件的引入将为抗癌和抗病毒药物发现领域中感兴趣的生物靶标提供新的相互作用的机会。通过针对这些核苷，这种合作将为加拿大人带来低成本和本地生产的药物，同时帮助培养年轻的科学头脑，否则他们将没有机会参与本科阶段的高影响力工业合作。